Successful selection of clinically effective oncolytic agents depends on the use of cells or tissues that accurately model target tumors, white being routinely reproducible in the laboratory. Recent work has provided evidence that three dimensional associations of extracellular matrix nanofibrils and the cellular architecture they induce are critical to development of in vitro systems that sufficiently mimic the physiological patterns of cell adhesion, cytoskeletal organization, signal transduction and gene expression, morphogenesis and differentiation in cultures of both normal and transformed cells. A number of analytical methods, including Gene Expression Profiling (GEP), proteomics and analyses of cellular function have demonstrated that 3D cultures are generally better tumor models than are monolayer cultures (Birgersdotter et al. (2005) Semin Cancer Bio. 15:405-412; Nelson and Bissell (2005) Semin Cancer Biol 15:342-352).